Chloride Balance in Preterm Infants during the First Week of Life

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Chloride Balance in Preterm Infants during the First Week of Life

Silvia Iacobelli, Elsa Kermorvant-Duchemin, Francesco Bonsante, Alexandre Lapillonne, Jean-Bernard Gouyon

To cite this version:

Silvia Iacobelli, Elsa Kermorvant-Duchemin, Francesco Bonsante, Alexandre Lapillonne, Jean-Bernard

Gouyon. Chloride Balance in Preterm Infants during the First Week of Life. International Journal

of Pediatrics, Hindawi Publishing Corporation, 2012, 2012, pp.931597. �10.1155/2012/931597�. �hal-

01194223�

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Volume 2012, Article ID 931597, 7 pages doi:10.1155/2012/931597

Clinical Study

Chloride Balance in Preterm Infants during the First Week of Life

Silvia Iacobelli, ^{1, 2} Elsa Kermorvant-Duchemin, ^{3, 4} Francesco Bonsante, ^{1, 2} Alexandre Lapillonne, ^{3, 4} and Jean-Bernard Gouyon ^{1, 2, 5}

1 Neonatology and NICU, GHSR, CHR, BP 350, 97448 Saint Pierre Cedex, R´eunion, France

2 Centre d’Etudes Périnatales de l’Océan Indien, Centre d’Investigation Clinique et d’Epidémiologie Clinique (CIC-EC) CHR, 97410 Saint Pierre, Réunion, France

3 Department of Neonatology, AP-HP, Groupe Hospitalier Cochin-Saint-Vincent de Paul, 75014 Paris, France

4 Paris Descartes University, 75270 Paris, France

5 NICU, Department of Paediatrics, University of Dijon, 21034 Dijon Cedex, France

Correspondence should be addressed to Silvia Iacobelli, silvia.iacobelli@chr-reunion.fr Received 21 November 2011; Revised 15 December 2011; Accepted 15 December 2011 Academic Editor: Alan Richard Spitzer

Copyright © 2012 Silvia Iacobelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. To describe the chloride balance in infants born 25–32-week gestation, analyze the association of chloride changes with hydroelectrolytic status and their relationship with perinatal conditions, morbidities, and neurological outcome. Methods. For 7 days after birth, sodium and chloride balance, plasma potassium, phosphate, and total carbon dioxide (tCO 2 ) were prospectively determined and strong ion diﬀerence (SID) calculated. Three multivariate regression analyses were performed to identify factors associated with high plasma chloride concentration, low SID, and low tCO 2 . Results. 107 infants were studied. Plasma chloride concentration was significantly positively associated with plasma sodium concentration. Higher plasma chloride and lower SID were significantly associated with lower plasma tCO 2 . Chloride intake was the main independent factor associated with high plasma chloride, low SID, and low plasma tCO 2 , with lesser contribution of sodium intake and low gestational age (GA). Also, patent ductus arteriosus and birth weight loss were independent factors aﬀecting plasma chloride and SID. Neither high chloride levels nor low SID were associated to impaired neurological outcome. Conclusions. In preterm infants, chloride balance is influenced by GA and by interrelationship between sodium and chloride intake. High chloride levels are associated with metabolic acidosis but not related to increased risk of impaired neurological outcome.

1. Introduction

Transition to the extrauterine environment is associated with major changes of body water and salt composition in the premature baby [1]. Changes in plasma sodium concentra- tions have been particularly studied, and large variations in sodium levels have shown a relationship with impaired outcome [2]. On the contrary, metabolism of chloride (Cl ⁻ ), the major anion of the extracellular fluids, has been rarely investigated. Even if chloride balance usually parallels that of sodium, and so it is strictly correlated to the extracellular volume balance, chloride losses and excretion can also occur independently from sodium, mainly in equilibrium with bicarbonate status. Therefore, hyperchloraemia is often asso- ciated with metabolic acidosis, a causative factor for intra- ventricular haemorrhage and other morbidities in preterm

babies [3]. The concept of “strong ion di ﬀ erence” (SID) is

used to help explain “metabolic” acid base abnormalities as-

sociated with changes in chloride concentration [4]. Accord-

ing to the “Stewart’s approach,” three independent variables

determine pH in plasma, by changing the degree of water

dissociation into hydrogen ions. These three variables are the

SID, the partial pressure of carbon dioxide CO 2 (pCO 2 ), and

the total concentration of week acids (primary albumin). A

decrease in the SID will result in an acidifying eﬀect on plas-

ma. The SID is calculated as the charge diﬀerence between

the sum of measured strong cations (Na ⁺ , K ⁺ , Ca ²⁺ , and

Mg ²⁺ ) and measured strong anions (Cl ⁻ , lactate) [5]. A

strong ion is defined as one that is almost completely dis-

sociated at physiological pH. As both Na ⁺ and Cl ⁻ are the

major strong ions in plasma, the SID calculated as the sim-

ply di ﬀ erence between sodium and chloride represents one

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2 International Journal of Pediatrics

independent variable determining the hydrogen ion and the bicarbonate ion concentrations; an increase in the plasma Cl ⁻ relative to Na ⁺ decreases the plasma SID and lowers the pH [6].

To our knowledge, no study has explored the chloride balance during the first week of life or the impact of changes in plasma chloride levels on perinatal morbidity and neuro- logical outcome in preterm infants. The present investigation was carried out to enlighten these two points.

2. Patients and Methods

2.1. Study Population. From January 2007 to May 2008 all consecutive infants born below 33 weeks of gestational age (GA) and admitted to the neonatal intensive care unit (NICU) of Dijon University Hospital within 6 hours after birth were eligible. Noninclusion criteria were major congen- ital anomalies. A criterion for secondary exclusion was death within the first week.

The research protocol was authorized by the Ethics Com- mittee of the Hospital. Informed, signed parental consent was obtained.

Parenteral nutrition (PN) was administered by eight dif- ferent PN bags commercially batch produced with increasing nutrient intake for day 1 to day 7 of life in infants with cen- tral venous line [7]. Infants without central venous line also received PN by commercially batch-produced bags at lower osmolarity and nutrient intake. 10% dextrose or sterile water for injection at choice could be added to PN bags by retro- grade continuous infusion in order to achieve the required water supply. Guidelines for daily prescription of water were provided. These guidelines recommended starting fluid intake at 80 mL/kg/day and then giving fluid input to allow a daily weight loss from 2 to 4% and to maintain plas- ma sodium and potassium concentrations within 135 to 145 mmol/L and 4–6 mmol/L, respectively [8]. Starting sod- ium, potassium- and chloride intake was at day 3.

In the purpose to assess short- and middle-term neu- rological outcome in this population, cerebral ultrasounds were realized during the infant hospital stay and neurological examination at 18 months of corrected age.

Cranial ultrasounds were performed by experienced ex- aminers (neonatologists or radiologists) according to the fol- lowing protocol: day 1, 3, 7, 10, 15, and then at least every 2 weeks or more often as clinically indicated, until discharge.

Severe abnormal cerebral ultrasound was defined as severe (grade 3 or 4) intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (c-PVL) occur- ring before infants discharge from hospital. IVH was graded at cerebral ultrasound according to Papile et al. [9]. c-PVL was defined by cranial ultrasound as an area of increased echogenicity of the periventricular white matter in acute phase which subsequently evolved into cystic lesion [10].

Children were subjected to a detailed physical and neuro- logical examination at 18 months of corrected age, in order to assess tone, reflexes, posture, and movements. We used the definition of cerebral palsy proposed by the European Cere- bral Palsy Network [11].

2.2. Data Collection. For the 7 days after birth, plasma sodi- um, potassium, chloride, phosphate, and total carbon diox- ide (tCO 2 ) were determined daily. We daily calculated the plasma SID as the diﬀerence between sodium and chloride.

Base excess (BE), bicarbonate (HCO 3 ⁻ ), pCO 2 , and pH were performed according to clinician decision.

Day 1 data were obtained on a blood sample taken at 12 hours of life. Day 2 blood sample was taken 24 hours later.

Sodium, potassium, and chloride intake from intra- venous, oral fluids and drugs administration during the study period was recorded from the infant chart. Intravenous flushes and sodium and chloride administration by drugs, or transfusions were taken into account when calculating fluid and electrolyte intake.

Daily, consecutive 8-hour urine collection starting 4 hours before the blood sampling was performed by using a plastic bag. Urine was analyzed for sodium and chloride con- centrations. Plasma and urine sodium and chloride, plasma potassium, phosphate, and tCO 2 concentrations were mea- sured by an Ortho Clinical Diagnostic analyzer (Rochester, USA), which uses direct potentiometry. Blood gas was ana- lyzed on the Radiometer ABL 700 blood gas analyzer.

Chloride and sodium balance were defined, respectively, as the diﬀerence between chloride intake and urinary excre- tion and sodium intake and urinary excretion was expressed as mmol/kg/day.

2.3. Statistics. Data from categorical variables were analyzed using χ ² test or Fisher exact test for small samples. Continu- ous variables were expressed as mean ± standard deviation, and diﬀerences between groups were analysed using ANOVA or Kruskal-Wallis analysis of variance for not normally dis- tributed data. Statistical tests were performed with SAS soft- ware 8.2. Results were considered statistically significant at a 5% level.

We measured the relationship between both plasma chlo- ride concentration and plasma SID with plasma sodium, phosphate, tCO2, pH, BE, and HCO 3 ⁻ .

Furthermore, we realized for each of the following para- meters (plasma chloride concentration, plasma SID, and tCO 2 ) a univariate analysis of variance in order to explore their association with water, energy, amino acids, phosphate, sodium, potassium, and chloride intakes and also their association with all the perinatal variables summarized in Table 1. For each of the above parameters, variables signi- ficant at a P level < 0.20 at the univariate analysis were entered into a backward selection analysis of variance.

3. Results and Discussion

3.1. Results. During the study period, 147 neonates born below 33 weeks of gestation were hospitalized in our NICU.

Of these, 129 were admitted within the 6th hour of life.

Among them, 12 were not enrolled in the study: 1 due to

major congenital anomalies, 9 due to omission of the attend-

ing physician, and 2 due to refused parental consent. So, 117

infants were entered into the study. Among them, 10 were

excluded secondary: 2 because they died during the first

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Table 1: Characteristics of 107 infants <33 weeks of GA hospital- ized in NICU.

Characteristics at birth %

Male gender 54.2

BW 1316 ± 361 ^¤

GA 30.0 ± 1.6 ^#

SGA 25.4

Apgar score <3 at 1 minute of life 11.2 Prenatal characteristics

Antenatal steroids 77.6

Caesarean section 79.4

Postnatal characteristics

Central venous line 62.6

Acute anaemia at birth 13.2

Body weight loss >15% of BW 11.2

RDS-requiring surfactant 66.4

Early onset sepsis 6.5

Hypotension-requiring treatment 13.1

Acute renal failure ^∗ 11.2

HsPDA 36.4

Oxygen dependency beyond 36 wks PCA 12.3

Necrotizing enterocolitis 2.8

Severe abnormal cerebral ultrasound ^† 1.8

Death after the first week of life 0

Cerebral palsy at 18 months of PCA 2.1 (NICU) Neonatal Intensive Care Unit; (BW) birth weight; (GA) gestational age; (SGA) small for gestational age; (RDS) respiratory distress syndrome;

(HsPDA) hemodynamically significant patent ductus arteriosus; (PCA) postconceptional age.

¤ g (mean ± SD), ^# weeks (mean ± SD), ^∗ according to [12], ^† intraventricular haemorrhage grade 3 or 4 and/or periventricular leukomalacia.

week, 2 as they were transferred to other units, and 6 due to diﬃculties of blood sampling. Finally, 107 infants were en- tered into the study. Table 1 shows antenatal and postnatal characteristics of the study population.

Chloride concentration values were available for 95, 96, 98, 98, 91, 92, and 88% of infants, and sodium concentration values were available for 98, 100, 99, 99, 95, 95, and 92% from day 1 to 7. tCO ₂ values were available for 87, 83, 86, 87, 83, 83, and 77% of infants from day 1 to 7. Arterial blood gas was performed in 37% of the blood samples; when these data were available, the analysis showed that plasma chloride and SID were significantly associated with tCO 2 , BE, and HCO 3 ⁻

and that tCO 2 was the main factor independently associated with higher plasma chloride and lower SID. Therefore, tCO 2

was the biochemical parameter used to express the results concerning the relationship of chloride with metabolic acid base balance.

Figure 1 shows the chloride and sodium intake, urinary excretion and balance during the study period. Figure 2 shows plasma chloride percentiles during the first week of life in the study population. The mean plasma chloride value during the study period was 110.5 ± 5.0 mmol/L. Chloride concentration was equal or above 120 mmol/L in 4% of

plasma samples and in 14% of patients. Hypernatraemia de- fined as plasma sodium >150 mmol/L occurred in 1.9% of infants.

Plasma chloride and sodium profiles were similar, while urinary chloride concentration did not parallel urinary sodi- um excretion (Figure 1).

Figure 3 shows the evolution of the plasma SID during the first week of life.

Plasma chloride concentration was strongly positively associated with plasma sodium concentration ( r ² = 0 . 66; P <

0 . 000001); a negative significant association was described with plasma tCO ₂ ( r ² = 0 . 13; P < 0 . 01) and phosphate ( r ² = 0 . 05; P < 0 . 05). Plasma SID was significantly positively asso- ciated with plasma tCO 2 (r ² = 0.28; P < 0.001) and phos- phate (r ² = 0.11; P < 0.01).

Clinical factors associated with plasma chloride concen- tration at the univariate analysis were weight loss % of birth weight (BW), GA, acute anaemia at birth, respiratory dis- tress syndrome (RDS) requiring surfactant, hypotension requiring treatment, hemodynamically significant patent ductus arteriosus (hsPDA), acute renal failure, intraventric- ular haemorrhage (IVH) grade 3-4, necrotizing enterocolitis (stage 2 or more of the Bell classification), chloride, sodium, phosphate, amino acid, and water intakes and day of life (data not shown). Among them, chloride intake, hsPDA, weight loss % of BW, sodium intake, and GA remained inde- pendent factors associated with plasma chloride at the multi- variate analysis (Table 2). Factors associated with plasma SID at the univariate analysis were GA, acute anaemia at birth, RDS-requiring surfactant, hypotension requiring treatment, IVH grade 3-4, hsPDA, chloride, sodium, phosphate, and amino acid intake, and day of life (data not shown). Among them, chloride intake, hsPDA, sodium intake, phosphate intake and GA remained independent factors associated with plasma SID at the multivariate analysis (Table 2).

Factors associated with lower plasma tCO 2 at the univari- ate analysis were GA, RDS requiring surfactant, hypotension requiring treatment, hsPDA, low Apgar score at 1 minute of life, sodium, chloride, phosphate and amino acid intake and day of life (data not shown). Among them, chloride and sod- ium intakes and GA remained independent factors associated with plasma tCO 2 at the multivariate analysis (Table 2).

3.2. Discussion. To our knowledge this is the first prospective

study showing the chloride balance in very preterm infants

during the first week of life. Our data found a strong link

between chloride and sodium metabolism. These results are

consistent with others; Day et al. [13] showed that in very

low birth weight infants (VLBWI) who developed hypo-

natraemia during the second and the third week of life,

plasma chloride concentration paralleled plasma sodium,

and this also occurred in sodium supplemented VLBWI be-

tween 2 and 6 weeks of age [14]. In the same infants chloride

excretion in urine did not parallel that of sodium [14]. Our

results also showed that urinary chloride excretion is inde-

pendent from that of sodium since the first week of postnatal

life. In our series weight loss % of BW was one of the clinical

factors significantly associated to high chloride levels. This

confirms that the strict correlation between sodium and

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4 International Journal of Pediatrics Chloride balance

Intake Balance

Excretion

(mmol/kg/da y)

− 6

− 4

− 2 0 2 4 6

− 1 . 8

− 2 . 8

− 0 . 8 ⁻ 0 . 3 0.2 0.1 0.1

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

(a) Sodium balance

− 2 ₋ 3 . 4

− 1 . 3 ⁻ 0 . 4 0.2 0.3 0.8

(mmol/kg/da y)

− 6

− 4

− 2 0 2 4 6

Intake Balance

Excretion

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

(b)

U Cl

P Na/Cl ratio (%) U Na/Cl ratio (%) 0

20 40 60 80 100 120 140

0 2 4 6 8 10 12 14

U Na

(mmol/kg/da y)

(%)

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

(c)

Figure 1: Chloride and sodium intake and balance during the first week of life in 107 infants <33 weeks of GA hospitalized in NICU.

chloride metabolism depends on parallel sodium and chlo- ride changes due to the extracellular volume contraction after birth.

Our study also disclosed a wide variability of chloride levels during the first week of life with mean plasma concen- trations much higher when compared to the range usually

considered as normal for preterm babies [15]. Higher chlo- ride levels were detected in infants with lower GA. As re- ported by others [16], higher plasma chloride concentration and signs of metabolic acidosis (low SID and tCO 2 ) were sig- nificantly associated with higher chloride intake in our study.

Previous reports have already shown that a reduction in

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95 100 105 110 115 120 125

(mmol/L)

Plasma chloride percentiles

97th 90th 75th 50th 25th 10th 3rd

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

112.5 106 99.5

116.6 108.7 100.7

119.3 111.9 104.4

120 112.5

105 121.3 112.4 103.5

121.8 111.7 101.6

121.1 110.6 100.2

97th percentile 50th percentile 3rd percentile

Figure 2: Plasma chloride percentiles during the first week of life in 107 infants <33 weeks of GA hospitalized in NICU (P value = 0.000001 at Kruskal-Wallis one-way analysis of variance).

22 24 26 28 30 32 34

28.7 29.8 28.9

28 27.7 27.3 27.9

SID during the first week of life

SID (mmol/L)

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Figure 3: Strong ion diﬀerence (SID) during the first week of life in 107 infants <33 weeks of GA hospitalized in NICU (P value = 0.000001 at Kruskal-Wallis one way analysis of variance).

the chloride load by using acetate salts can be safely achieved and may even decrease plasma chloride levels and metabolic acidosis in preterm infants on PN during the first days of life [17, 18]. Groh-Wargo et al. underlined the e ﬀ ect of chloride from normal saline flushes in increasing the total chloride load in LBWI on PN [16]. Our results showed in addition that higher sodium and phosphate intake was associated to lower plasma chloride and lower metabolic acidosis in pre- term infants on PN. The above suggests that sodium given in a salt formulation not containing chloride may be protective against metabolic acidosis and high chloride levels, and that the interrelationship between sodium and chloride intakes should be looked at as it can interfere with acid base home- ostasis. Concerning the inverse association of phosphate in- take and metabolic acidosis, we speculate that this could depend on the fact that dietary phosphate intake may aﬀect renal regulation of plasma bicarbonate and so the renal de- fence against metabolic acidosis, as already proven in animal

Table 2: Factors associated with plasma chloride (mmol/L), SID, and tCO 2 levels (mmol/L) at multivariate analysis in 107 infants <33 weeks of GA.

P value Incremental r ² Beta coeﬃcient Plasma chloride ^∗

Chloride intake <0.001 0.14 +

HsPDA <0.01 0.03 +

Sodium intake <0.01 0.02 −

Weight loss % of

BW <0.01 0.02 +

GA <0.05 0.01 ₋

SID ^∗∗

Chloride intake <0.001 0.09 −

HsPDA <0.01 0.04 −

Sodium intake <0.05 0.01 +

Phosphate intake < 0.05 0.01 +

GA <0.05 0.01 +

tCO 2 ∗∗∗

Chloride intake <0.001 0.13 −

GA <0.01 0.02 +

Sodium intake <0.05 0.01 +

(SID) strong ion di ﬀ erence; (tCO ₂ ) total carbon dioxide; (hsPDA) hemo- dynamically significant patent ductus arteriosus; (BW) Birth weight; (GA) gestational age;

∗ General r ² = 0 . 22; ^∗∗ General r ² = 0 . 16 ^∗∗∗ General r ² = 0 . 16.

models and adults [19]. Of course this point needs to be investigated in future prospective studies.

Even if no previous studies have specifically explored the

association of changes in plasma chloride levels and neona-

tal neurological morbidities, concerns have been expressed

about the finding that blood chloride concentration had a

significant linear correlation with metabolic acidosis, which

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6 International Journal of Pediatrics

is thought to be a causative factor in intraventricular hae- morrhage in preterm [3]. Moreover, plasma chloride concen- tration has also a strong correlation with plasma sodium con- centration, and several retrospective investigations focused on natraemia have reported that changes in sodium levels, as well neonatal hyper- or hyponatraemia, were associated to increased risk of severe cerebral haemorrhage and cerebral palsy [2, 20].

This cohort of very preterm infants provided important additional information, as in our study the only clinical vari- able associated with both high chloride levels and low SID was hsPDA, and this could be explained as infants with this pathological condition may exhibit metabolic acidosis [21].

Neither high chloride levels nor low SID were associated to impaired neurological outcome (severe abnormal cerebral ultrasound or cerebral palsy). It is worthy to note that the incidence of hypernatraemia was very low in our study, espe- cially when compared to previous reports [22, 23].

Finally it is interesting to remind that chloride depletion too may represent a contributing cause of morbidity and mortality in preterm populations, as proven by human and animals studies [24, 25], but in our cohort low chloride levels were not correlated to increased morbidity.

The low incidence of electrolyte disturbance-related morbidity in our population was probably due to careful management of fluid and electrolyte balance advocated by the unit guidelines and based on the strict monitoring of infants hydroelectrolytic status.

4. Conclusion

This study allowed describing the postnatal chloride balance in preterm infants hospitalized in NICU. Plasma chloride levels during the first week are higher in infants born at lower GA, and they are correlated with plasma sodium levels and biological markers of metabolic acidosis. In this carefully monitored population, changes in plasma chloride levels were not associated to poor neurological outcome in the short and middle term.

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Chloride Balance in Preterm Infants during the First Week of Life

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Chloride Balance in Preterm Infants during the First Week of Life

Silvia Iacobelli, Elsa Kermorvant-Duchemin, Francesco Bonsante, Alexandre Lapillonne, Jean-Bernard Gouyon

To cite this version:

Silvia Iacobelli, Elsa Kermorvant-Duchemin, Francesco Bonsante, Alexandre Lapillonne, Jean-Bernard

Gouyon. Chloride Balance in Preterm Infants during the First Week of Life. International Journal

of Pediatrics, Hindawi Publishing Corporation, 2012, 2012, pp.931597. �10.1155/2012/931597�. �hal-

01194223�

Volume 2012, Article ID 931597, 7 pages doi:10.1155/2012/931597

Clinical Study

Chloride Balance in Preterm Infants during the First Week of Life

Silvia Iacobelli, 1, 2 Elsa Kermorvant-Duchemin, 3, 4 Francesco Bonsante, 1, 2 Alexandre Lapillonne, 3, 4 and Jean-Bernard Gouyon 1, 2, 5

1 Neonatology and NICU, GHSR, CHR, BP 350, 97448 Saint Pierre Cedex, R´eunion, France

2 Centre d’Etudes Périnatales de l’Océan Indien, Centre d’Investigation Clinique et d’Epidémiologie Clinique (CIC-EC) CHR, 97410 Saint Pierre, Réunion, France

3 Department of Neonatology, AP-HP, Groupe Hospitalier Cochin-Saint-Vincent de Paul, 75014 Paris, France

4 Paris Descartes University, 75270 Paris, France

5 NICU, Department of Paediatrics, University of Dijon, 21034 Dijon Cedex, France

Correspondence should be addressed to Silvia Iacobelli, silvia.iacobelli@chr-reunion.fr Received 21 November 2011; Revised 15 December 2011; Accepted 15 December 2011 Academic Editor: Alan Richard Spitzer

Copyright © 2012 Silvia Iacobelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

babies [3]. The concept of “strong ion di ﬀ erence” (SID) is

used to help explain “metabolic” acid base abnormalities as-

sociated with changes in chloride concentration [4]. Accord-

ing to the “Stewart’s approach,” three independent variables

determine pH in plasma, by changing the degree of water

dissociation into hydrogen ions. These three variables are the

SID, the partial pressure of carbon dioxide CO 2 (pCO 2 ), and

the total concentration of week acids (primary albumin). A

decrease in the SID will result in an acidifying eﬀect on plas-

ma. The SID is calculated as the charge diﬀerence between

the sum of measured strong cations (Na + , K + , Ca 2+ , and

Mg 2+ ) and measured strong anions (Cl − , lactate) [5]. A

strong ion is defined as one that is almost completely dis-

sociated at physiological pH. As both Na + and Cl − are the

major strong ions in plasma, the SID calculated as the sim-

ply di ﬀ erence between sodium and chloride represents one

2 International Journal of Pediatrics

independent variable determining the hydrogen ion and the bicarbonate ion concentrations; an increase in the plasma Cl − relative to Na + decreases the plasma SID and lowers the pH [6].

To our knowledge, no study has explored the chloride balance during the first week of life or the impact of changes in plasma chloride levels on perinatal morbidity and neuro- logical outcome in preterm infants. The present investigation was carried out to enlighten these two points.

2. Patients and Methods

The research protocol was authorized by the Ethics Com- mittee of the Hospital. Informed, signed parental consent was obtained.

In the purpose to assess short- and middle-term neu- rological outcome in this population, cerebral ultrasounds were realized during the infant hospital stay and neurological examination at 18 months of corrected age.

Cranial ultrasounds were performed by experienced ex- aminers (neonatologists or radiologists) according to the fol- lowing protocol: day 1, 3, 7, 10, 15, and then at least every 2 weeks or more often as clinically indicated, until discharge.

Children were subjected to a detailed physical and neuro- logical examination at 18 months of corrected age, in order to assess tone, reflexes, posture, and movements. We used the definition of cerebral palsy proposed by the European Cere- bral Palsy Network [11].

2.2. Data Collection. For the 7 days after birth, plasma sodi- um, potassium, chloride, phosphate, and total carbon diox- ide (tCO 2 ) were determined daily. We daily calculated the plasma SID as the diﬀerence between sodium and chloride.

Base excess (BE), bicarbonate (HCO 3 − ), pCO 2 , and pH were performed according to clinician decision.

Day 1 data were obtained on a blood sample taken at 12 hours of life. Day 2 blood sample was taken 24 hours later.

Chloride and sodium balance were defined, respectively, as the diﬀerence between chloride intake and urinary excre- tion and sodium intake and urinary excretion was expressed as mmol/kg/day.

We measured the relationship between both plasma chlo- ride concentration and plasma SID with plasma sodium, phosphate, tCO2, pH, BE, and HCO 3 − .

3. Results and Discussion

3.1. Results. During the study period, 147 neonates born below 33 weeks of gestation were hospitalized in our NICU.

Of these, 129 were admitted within the 6th hour of life.

Among them, 12 were not enrolled in the study: 1 due to

major congenital anomalies, 9 due to omission of the attend-

ing physician, and 2 due to refused parental consent. So, 117

infants were entered into the study. Among them, 10 were

excluded secondary: 2 because they died during the first

Table 1: Characteristics of 107 infants <33 weeks of GA hospital- ized in NICU.

Characteristics at birth %

Male gender 54.2

BW 1316 ± 361 ¤

GA 30.0 ± 1.6 #

SGA 25.4

Apgar score <3 at 1 minute of life 11.2 Prenatal characteristics

Antenatal steroids 77.6

Caesarean section 79.4

Postnatal characteristics

Central venous line 62.6

Acute anaemia at birth 13.2

Body weight loss >15% of BW 11.2

RDS-requiring surfactant 66.4

Early onset sepsis 6.5

Hypotension-requiring treatment 13.1

Acute renal failure ∗ 11.2

HsPDA 36.4

Silvia Iacobelli, ^{1, 2} Elsa Kermorvant-Duchemin, ^{3, 4} Francesco Bonsante, ^{1, 2} Alexandre Lapillonne, ^{3, 4} and Jean-Bernard Gouyon ^{1, 2, 5}

the sum of measured strong cations (Na ⁺ , K ⁺ , Ca ²⁺ , and

Mg ²⁺ ) and measured strong anions (Cl ⁻ , lactate) [5]. A

sociated at physiological pH. As both Na ⁺ and Cl ⁻ are the

independent variable determining the hydrogen ion and the bicarbonate ion concentrations; an increase in the plasma Cl ⁻ relative to Na ⁺ decreases the plasma SID and lowers the pH [6].

Base excess (BE), bicarbonate (HCO 3 ⁻ ), pCO 2 , and pH were performed according to clinician decision.

We measured the relationship between both plasma chlo- ride concentration and plasma SID with plasma sodium, phosphate, tCO2, pH, BE, and HCO 3 ⁻ .

BW 1316 ± 361 ^¤

GA 30.0 ± 1.6 ^#

Acute renal failure ^∗ 11.2

Severe abnormal cerebral ultrasound ^† 1.8

¤ g (mean ± SD), ^# weeks (mean ± SD), ^∗ according to [12], ^† intraventricular haemorrhage grade 3 or 4 and/or periventricular leukomalacia.

Plasma chloride concentration was strongly positively associated with plasma sodium concentration ( r ² = 0 . 66; P <

0 . 000001); a negative significant association was described with plasma tCO ₂ ( r ² = 0 . 13; P < 0 . 01) and phosphate ( r ² = 0 . 05; P < 0 . 05). Plasma SID was significantly positively asso- ciated with plasma tCO 2 (r ² = 0.28; P < 0.001) and phos- phate (r ² = 0.11; P < 0.01).

− 0 . 8 ⁻ 0 . 3 0.2 0.1 0.1

− 2 ₋ 3 . 4

− 1 . 3 ⁻ 0 . 4 0.2 0.3 0.8